Errores innatos de la inmunidad: ¿Qué debe saber y cuándo debe sospechar el otorrinolaringólogo? / Inborn errors of immunity: What should the otolaryngologist know, and when to suspect them?

Introducción: Los errores innatos de la inmunidad, previamente conocidos como inmunodeficiencias primarias, son un grupo heterogéneo de patologías cuya presentación clínica incluye infecciones recurrentes, persistentes o refractarias al tratamiento en el campo de la otorrinolaringología. Materiales y métodos: Se realizó una revisión narrativa de la literatura a partir de la búsqueda de documentos en PUBMED y EMBASE. Discusión y conclusiones: Los pacientes con sospecha de error innato de la inmunidad requieren un diagnóstico temprano con el fin de disminuir las complicaciones a largo plazo, por lo que la valoración y el abordaje inicial desempeñan un papel fundamental en el reconocimiento de estas enfermedades.

Introduction: Inborn errors of immunity, previously known as primary immunodeficiencies, are a heterogeneous group of pathologies whose clinical presentation includes recurrent, persistent and/or refractory infections to treatment in otorhinolaryngology. Materials and methods: Narrative review of the literature was carried out from the search for articles in PUBMED and EMBASE. Discussion and conclusions: Patients with suspected inborn error of immunity require an early diagnosis to reduce long-term complications; the initial assessment and approach play a fundamental role in the recognition of these diseases

Supervivenciade pacientes pediátricos con inmunodeficiencias primarias en un hospital público del occidente de México / Survival of pediatric patients with primary immunodeficiencies in a public hospital in western Mexico

Se presenta una serie de casos de inmunodeficiencias primarias y se describen las variables asociadas a supervivencia en pacientes ≤ 16 años. Los diagnósticos fueron acordes a los criterios de la Unión Internacional de las Sociedades de Inmunología. Se realizó un análisis de supervivencia mediante curvas de Kaplan-Meier.Entre los años 2004 y 2019, se diagnosticaron 40 pacientes con inmunodeficiencias primarias. Las más frecuentes fueron inmunodeficiencias que afectaban la inmunidad celular y humoral, el 32,5 %, y deficiencias predominantemente de anticuerpos, el 32,5 %. La mediana de edad al inicio de los síntomas y al momento del diagnóstico fue de 3,01 y 10,4 meses, respectivamente. Fallecieron el 35 % y el riesgo fue mayor en pacientes con inmunodeficiencias que afectaban la inmunidad celular y humoral y en quienes presentaron manifestaciones clínicas y tuvieron el diagnóstico en los primeros seis meses de vida.

A case series of primary immunodeficiencies is presented and outcome measures associated with survival among patients ≤ 16 years old are described. Diagnoses were made based on the criteria by the International Union of Immunological Societies. Survival was analyzed using Kaplan-Meier curves.Between 2004 and 2019, 40 patients were diagnosed with primary immunodeficiencies. The most common were immunodeficiencies affecting humoral and cell-mediated immunity (32.5 %) and predominantly antibody deficiencies (32.5 %). The median age at the onset of symptoms and at the time of diagnosis was 3.01 and 10.4 months, respectively. Thirty-five percent of patients died, and the risk was higher among those with immunodeficiencies affecting humoral and cell-mediated immunity and those who developed clinical manifestations and were diagnosed in the first 6 months of life

Inmunodeficiencias primarias: un reto para la inmunogenética / Primary immunodeficiencies: a challenge for immuno-genetics

Las inmunodeficiencias primarias constituyen un grupo de más de 300 enfermedades frecuentemente graves y a menudo mortales que reflejan un déficit cuantitativo o cualitativo en uno o más componentes del sistema inmunitario. Son el resultado de defectos genéticos heredados que suelen afectar a 1 de cada 8000 a 10 000 nacidos vivos. Las manifestaciones clínicas suelen ser muy variadas, debido a que en su mayoría presentan una amplia heterogeneidad genética: infecciones (comunes recurrentes, comunes graves, o raras y graves), inflamación, autoinmunidad, malignidad o alergia. Teniendo en cuenta que a los profesionales médicos de diversas especialidades les resulta difícil identificar cuándo están en presencia de una IDP, nos proponemos describir las características clínicas, epidemiológicas, inmunitarias y genéticas de las inmunodeficiencias primarias. Para la realización de la revisión bibliográfica se utilizaron 27 referencias bibliográficas(AU)

Primary immunodeficiencies constitute a group of more than 300 frequently serious and often fatal diseases that reflect a quantitative and / or qualitative deficit in one or more components of the immune system. They are the result of inherited genetic defects that usually affect 1 in 8,000 to 10,000 live births. The clinical manifestations are usually very varied, because they mostly have a wide genetic heterogeneity, they can be caused by infections (common recurring, common serious, or rare and serious), inflammation, autoimmunity, malignancy, or allergy. Given that medical professionals of various specialties find it difficult to identify when they are in the presence of an primary immunodeficiency, it is proposed as an objective: to describe the clinical, epidemiological, immunological and genetic characteristics of Primary immunodeficiency. For the literature review, 27 bibliographic references were used(AU)

Recuento poblacional linfocitario como primera aproximación al diagnóstico de inmunodeficiencias primarias / Lymphocyte population count as a first approach to the diagnosis of primary immunodeficiencies

RESUMEN Las inmunodeficiencias primarias (IDP) se caracterizan por alteraciones de los componentes del sistema inmunitario. El recuento poblacional linfocitario por citometría de flujo es una aproximación al diagnóstico molecular y se expresa por inmunofenotipos. El objetivo del estudio fue describir el recuento poblacional linfocitario y los inmunofenotipos compatibles con IDP en pacientes con sospecha de IDP en un hospital de referencia nacional peruano. Se revisaron los registros de 261 casos que cumplían con los criterios de sospecha clínica para IDP de la Jeffrey Modell Foundation entre abril y diciembre de 2016. De los 261 casos con sospecha de IDP se hallaron 54,8% de varones. Se encontró 93 pacientes (35,6%) con inmunofenotipos compatibles con alguna IDP. El inmunofenotipo de inmunodeficiencia común variable fue más frecuente (36,6%), seguido de agammaglobulinemias (18,3%). Las deficiencias de anticuerpos fueron las IDP más frecuentes. Es necesario realizar otras pruebas moleculares para el diagnóstico genético específico.

ABSTRACT Primary immunodeficiencies (PID) are characterized by alterations in the components of the immune system. The lymphocyte population count by flow cytometry is an approach to molecular diagnosis and is expressed by immunophenotypes. The objective of the study was to describe the lymphocyte population count and immunophenotyping compatible with PID in patients with suspected PID in a Peruvian national reference hospital. Records of 261 cases meeting the Jeffrey Modell Foundation's PID clinical suspicion criteria were reviewed between April and December of 2016. Of the 261 suspected cases of PID, 54.8% were males. We found 93 patients (35.6%) with PID-compatible immunophenotyping. The common variable immunodeficiency immunophenotype was the most frequent (36.6%), followed by agammaglobulinemias (18.3%). Antibody deficiencies were the most common PID. Other molecular tests are needed for a specific genetic diagnosis.

Utilização do exoma na identificação de variantes genéticas relacionadas as Imunodeficiências Primárias (PIDs) / Using the exome to identify genetic variants related to Primary Immunodeficiencies (PIDs)

As imunodeficiências primárias (PIDs) são doenças genéticas que têm como principal característica alterações do sistema imune, caracterizadas por deficiências de desenvolvimento e/ou função desse sistema, levando o paciente à maior suscetibilidade às infecções de repetição, doenças auto-imunes e/ou neoplasias. Estão agrupadas como um único grupo de doenças e a sua classificação, varia de acordo com a natureza da deficiência imunológica subjacente, podendo ser por deficiências de anticorpos, imunodeficiências combinadas, desordens de células fagocitárias, entre outras. Estimam-se sua incidência entre 1:2.000 crianças nascidas vivas e o diagnóstico precoce dessas doenças, é essencial para a redução da morbidade e mortalidade desses pacientes. A identificação precoce e o tratamento eficiente das PIDs são pontos chaves para a sobrevivência e melhor qualidade de vida dos pacientes imunodeficientes, modificando de maneira decisiva o prognóstico destas doenças. Na busca de um diagnóstico mais rápido e eficaz, esse trabalho dispôs de uma análise multigênica de pacientes com pelo menos 1 dos 10 sinais de alerta para PID. Foram sequenciados e analisados 34 casos, sendo 25 do sexo masculino e 9 do sexo feminino. Utilizou-se ferramentas de nova geração e filtros específicos, baseados nos resultados do sequenciamento total do exoma, possibilitando assim , o diagnóstico de 7 casos de Agamaglobulinemia (gene BTK), 2 casos de Wiskott-Aldrich (gene WAS), 1 caso de Doença Granulomatosa Crônica (gene CYBB), 1 caso de Síndrome de Hiper-IgM do tipo I (gene CD40LG) e a investigação parental dos 23 casos sem diagnóstico concluído. Esses achados foram confirmados através do Sequenciamento de Sanger, considerado como padrão ouro para o estudo.

Primary immunodeficiencies are genetic diseases that have as main characteristic alterations of the immune system, characterized by deficiencies of development and / or function of this system, leading the patient to greater susceptibility to recurrent infections, autoimmune diseases and / or neoplasias. They are grouped as a single group of diseases and their classification varies according to the nature of the underlying immunological deficiency, and may be due to antibody deficiencies, combined immunodeficiencies, phagocytic cell disorders, among others. Their incidence is estimated between 1: 2000 live births and the early diagnosis of these diseases is essential to reduce the morbidity and mortality of these patients. Early identification and efficient treatment of PIDs are key points for the survival and better quality of life of immunodeficient patients, modifying the prognosis of these diseases in a decisive way. In the search for a faster and more effective diagnosis, this work had a multigenic analysis of patients with at least 1 of the 10 warning signs for PID. Thirty-four cases were sequenced and analyzed, of which 25 were male and 9 were female. New generation tools and specific filters were used based on the results of the complete exome sequencing, allowing the diagnosis of 7 cases of agammaglobulinemia (BTK gene), 2 cases of Wiskott-Aldrich (WAS gene), 1 case of disease Chronic Granulomatose (CYBB gene), 1 case of Type I Hyper-IgM Syndrome (CD40LG gene) and parental investigation of the 23 cases without a completed diagnosis. These findings were confirmed using the Sanger Sequencing, considered the gold standard for the study.